Biomedical subjects

Okihide Hikosaka

Publications and source records attributed to Okihide Hikosaka.

16 recordsLinked to original sources

PubMed2003

Reward-dependent gain and bias of visual responses in primate superior colliculus.

Eye movements are often influenced by expectation of reward. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual responses of monkey SC neurons increase when the visual stimulus indicates an upcoming reward. The increase occurred in two distinct manners: (1) reactively, as an increase in the gain of the visual response when the stimulus indicated an upcoming reward; (2) proactively, as an increase in anticipatory activity when reward was expected in the neuron's response field. These effects were observed mostly in saccade-related SC neurons in the deeper layer which would receive inputs from the cortical eye fields and the basal ganglia. These results, together with recent findings, suggest that the gain modulation may be determined by the inputs from both the cortical eye fields and the basal ganglia, whereas the anticipatory bias may be derived mainly from the basal ganglia.

Animals↗

PubMed2003

Effects of motivational conflicts on visually elicited saccades in monkeys.

The prospect of reward evoked by external stimuli is a central element of goal-oriented behavior. To elucidate behavioral effects of reward expectation on saccade latency, we employed a visually guided saccade task with asymmetrical reward schedule. The monkey had to make an immediate saccade to a peripheral visual target in every trial, but was rewarded for a correct saccade to only one of four possible target positions. Reward availability was predictable on the basis of the spatial position of the target throughout a daily session. Compared with the condition where all positions were rewarded with a smaller amount, the mean saccade latency in the asymmetrical reward schedule was significantly shorter when the saccade was made toward the position associated with reward than when it was directed to no-reward positions. Furthermore, a divergence-point analysis on cumulative latency distributions showed that the expectation of reward facilitated saccades at all latency ranges. In contrast, the expected lack of reward delayed the initiation of saccades with latencies longer than about 200 ms, irrespective of whether the saccade was made to a position orthogonal or opposite to the reward position. For saccades with latencies of more than approximately 240 ms, an additional delay was observed when the saccade was made to a position opposite, as compared to orthogonal, to the reward position. These results suggest that the facilitation by predictive reward is mediated by a preparatory process that is location-specific, whereas the inhibition by the absence of reward takes about 200 ms after the target onset to become effective and is initially location nonspecific but turns location-specific over time.

Animals↗

PubMed2003

Chunking during human visuomotor sequence learning.

Motor sequence learning is a process whereby a series of elementary movements is re-coded into an efficient representation for the entire sequence. Here we show that human subjects learn a visuomotor sequence by spontaneously chunking the elementary movements, while each chunk acts as a single memory unit. The subjects learned to press a sequence of 10 sets of two buttons through trial and error. By examining the temporal patterns with which subjects performed a visuomotor sequence, we found that the subjects performed the 10 sets as several clusters of sets, which were separated by long time gaps. While the overall performance time decreased by repeating the same sequence, the clusters became clearer and more consistent. The cluster pattern was uncorrelated with the distance of hand movements and was different across subjects who learned the same sequence. We then split a learned sequence into three segments, while preserving or destroying the clusters in the learned sequence, and shuffled the segments. The performance on the shuffled sequence was more accurate and quicker when the clusters in the original sequence were preserved than when they were destroyed. The results suggest that each cluster is processed as a single memory unit, a chunk, and is necessary for efficient sequence processing. A learned visuomotor sequence is hierarchically represented as chunks that contain several elementary movements. We also found that the temporal patterns of sequence performance transferred from the nondominant to dominant hand, but not vice versa. This may suggest a role of the dominant hemisphere in storage of learned chunks. Together with our previous unit-recording and imaging studies that used the same learning paradigm, we predict specific roles of the dominant parietal area, basal ganglia, and presupplementary motor area in the chunking.

Cluster Analysis↗

PubMed2003

Correlation of primate caudate neural activity and saccade parameters in reward-oriented behavior.

Changes in the reward context are associated with changes in neuronal activity in the basal ganglia as well as changes in motor outputs. A typical example is found in the caudate (CD) projection neurons and saccade parameters. It raised the possibility that the changes in CD neuronal activity contribute to the changes in saccade parameters. To examine this possibility, we calculated the correlation coefficients (CORs) of the firing rates of each neuron with saccade parameters (peak saccade velocity and latency) on a trial-by-trial basis. We then calculated the mean CORs separately for two CD populations: reward-enhanced type neurons (RENs) that showed enhanced activity and reward-depressed type neurons (RDNs) that showed depressed activity when reward was expected. The activity of RENs was positively correlated with the saccadic peak velocity and negatively correlated with the saccade latency. The activity of RDNs was not significantly correlated with the saccade parameters. We further analyzed the CORs for RENs, a major type of CD neurons. First, we examined the time courses of the CORs using a moving time window (duration: 200 ms). The positive correlation with the saccade velocity and the negative correlation with the saccade latency were present not only in the peri-saccadic period but also during the pre- and postcue periods. Second, we asked whether the CORs with the saccade parameters were direction-selective. A majority of RENs were more active before contralateral saccades (contralateral-preferring neurons) and their activity was correlated more strongly with contralateral saccades than with ipsilateral saccades. A minority of RENs, ipsilateral-preferring neurons, showed no such preference. These results are consistent with the hypothesis that CD neuronal activity exerts facilitatory effects on contralateral saccades and that the effects start well before saccade execution. Furthermore, a multiple regression analysis indicated that changes in activity of some, but not all, CD neurons could be explained by changes in saccade parameters; a major determinant was reward context (presence or absence of reward). These results suggest that, while a majority of CD neurons receive reward-related signals, only some of them can make a significant contribution to change saccadic outputs based on expected reward.

Animals↗

PubMed2002

Differential activation of monkey striatal neurons in the early and late stages of procedural learning.

The basal ganglia is a key structure for procedural learning. To examine in what aspects of procedural learning the basal ganglia participate, we recorded from striatal neurons (phasically active neurons) in monkeys while the animals were performing a sequential button press task (the 2 x 5 task) and compared the neuronal activity between two conditions: (1) while learning new sequences and (2) while executing overlearned sequences. Among 147 neurons recorded in two monkeys, 45 neurons were activated preferentially for new sequences (new-preferring neurons), 34 for overlearned sequences (learned-preferring neurons), and 68 were activated non-selectively (non-selective neurons). New-preferring neurons were more abundant in the "association" region [association striatum (AS); caudate nucleus and rostral putamen anterior to the anterior commissure], while the learned-preferring neurons were more abundant in the "sensorimotor" region [sensorimotor striatum (SM); putamen posterior to the anterior commissure]. In addition to the learning dependency, the AS and SM neurons were activated in different task periods: many AS neurons were activated during the delay period, while the SM neurons were more activated with reaching and button presses. These data, together with the data from our previous blockade study, suggest that the "association" and "sensorimotor" regions of the basal ganglia contribute preferentially to the early and late stages of procedural learning, respectively.

Animals↗

PubMed2002

A neural correlate of response bias in monkey caudate nucleus.

Primates are equipped with neural circuits in the prefrontal cortex, the parietal cortex and the basal ganglia that predict the availability of reward during the performance of behavioural tasks. It is not known, however, how reward value is incorporated in the control of action. Here we identify neurons in the monkey caudate nucleus that create a spatially selective response bias depending on the expected gain. In behavioural tasks, the monkey had to make a visually guided eye movement in every trial, but was rewarded for a correct response in only half of the trials. Reward availability was predictable on the basis of the spatial position of the visual target. We found that caudate neurons change their discharge rate systematically, even before the appearance of the visual target, and usually fire more when the contralateral position is associated with reward. Strong anticipatory activity of neurons with a contralateral preference is associated with decreased latency for eye movements in the contralateral direction. We conclude that this neuronal mechanism creates an advance bias that favours a spatial response when it is associated with a high reward value.

Action Potentials↗

PubMed2002

Visual and anticipatory bias in three cortical eye fields of the monkey during an adaptive decision-making task.

To examine the role of three cortical eye fields during internally guided decision-making processes, we recorded neuronal activities in the frontal eye field (FEF), supplementary eye field (SEF), and lateral intraparietal cortex (LIP) using a free-choice delayed saccade task with two synchronized targets. Although the monkeys must perform the task in a time-locked manner, they were free to choose either the receptive field (RF) target or the nonreceptive field (nRF) target to receive reward. In all three areas we found neurons with stronger activation during trials when the monkey was going to make a saccade to the RF target (RF trials) than to the nRF target (nRF trials). Modulation occurred not only during target presentation (visual bias) but also before target presentation (anticipatory bias). The visual bias was evident as an attenuated visual response to the RF stimulus in nRF trials. The anticipatory bias, however, was seen as an enhancement of pretarget activity in the RF trials. We analyzed the activity during the 500 msec before target presentation and found that 22.5% of FEF and 31.3% of LIP neurons and 49.1% of SEF neurons showed higher activity during the RF trials. To more accurately determine when each neuron started to show preferential activity, we used a new inverse interspike interval analysis procedure. Our results suggest that although all three cortical eye fields reflect attentional and intentional aspects of sensorimotor processing, SEF plays an earlier and perhaps more cognitive role in internally guided decision-making processes for saccades.

Adaptation, Physiological↗

PubMed2002

A neural correlate of oculomotor sequences in supplementary eye field.

Complex learned motor sequences can be composed of a combination of a small number of elementary actions. To investigate how the brain represents such sequences, we devised an oculomotor sequence task in which the monkey had to choose the target solely by the sequential context, not by the current stimulus combination. We found that many neurons in the supplementary eye field (SEF) became active with a specific target direction (D neuron) or a specific target/distractor combination (C neuron). Furthermore, such activity was often selective for one among several sequences that included the combination (S neuron). These results suggest that the SEF contributes to the generation of saccades in many learned sequences.

Animals↗

PubMed2002

Role of primate substantia nigra pars reticulata in reward-oriented saccadic eye movement.

To test the hypothesis that the basal ganglia are related to reward-oriented saccades, we examined activity of substantia nigra pars reticulata (SNr) neurons by using a one-direction-rewarded version of the memory-guided saccade task (1DR). Many SNr neurons changed (decreased or increased) their activity after and before a visual cue (post-cue and pre-cue activity). Post-cue decreases or increases tended to be larger to a contralateral cue. They were often modulated prospectively by the presence or absence of reward, either positively (enhanced in the rewarded condition) or negatively (enhanced in the nonrewarded condition). The positive reward modulation was more common among decreasing type neurons, whereas no such preference was observed among increasing type neurons. The reward-contingent decrease in SNr neuronal activity would facilitate rewarded saccades by inducing disinhibition in superior colliculus (SC) neurons. In contrast, the increase in SNr activity would suppress a saccade less selectively (rewarded or nonrewarded) by augmenting inhibition of SC neurons. The post-cue activity was often preceded by anticipatory pre-cue activity. Most typically, post-cue decrease was preceded by pre-cue decrease, selectively when the contralateral side was rewarded. This would reinforce the reward-oriented nature of SNr neuronal activity. The decreases and increases in SNr activity may be derived directly and indirectly, respectively, from the caudate (CD), where neurons show reward-contingent pre-cue and post-cue activity. These results suggest that the CD-SNr-SC mechanism would promote saccades oriented to reward.

Animals↗

PubMed2002

Feature-based anticipation of cues that predict reward in monkey caudate nucleus.

A subset of caudate neurons fires before cues that instruct the monkey what he should do. To test the hypothesis that the anticipatory activity of such neurons depends on the context of stimulus-reward mapping, we examined their activity while the monkeys performed a memory-guided saccade task in which either the position or the color of a cue indicated presence or absence of reward. Some neurons showed anticipatory activity only when a particular position was associated with reward, while others fired selectively for color-reward associations. The functional segregation suggests that caudate neurons participate in feature-based anticipation of visual information that predicts reward. This neuronal code influences the general activity level in response to visual features without improving the quality of visual discrimination.

Animals↗

PubMed2002

Central mechanisms of motor skill learning.

Recent studies have shown that frontoparietal cortices and interconnecting regions in the basal ganglia and the cerebellum are related to motor skill learning. We propose that motor skill learning occurs independently and in different coordinates in two sets of loop circuits: cortex-basal ganglia and cortex-cerebellum. This architecture accounts for the seemingly diverse features of motor learning.

Animals↗

PubMed2002

A new approach to the functional systems of the brain.

Action is the means by which animals survive. It consists of a complex combination of movements that are either innately endowed or acquired by learning. Innate and learned actions are controlled by different levels of neural networks: innate actions are controlled by reflex mechanisms and pattern generators in the spinal cord and brainstem, whereas learned actions are controlled by the cerebral cortex, basal ganglia, and cerebellum. However, these mechanisms are by no means independent. Recent studies have shown that multiple brain areas contribute to the implementation of learned actions. Based on a series of studies using a sequenced learning task with trial and error, we propose a hypothetical scheme in which a sequential procedure is acquired independently by two cortical systems, one using spatial coordinates, and the other using motor coordinates. They are active preferentially in the early and late stages of learning, respectively. Both of the systems are supported by loop circuits formed with the basal ganglia and the cerebellum, the former for reward-based evaluation and the latter for processing of timing. The proposed neural architecture would operate in a flexible manner to acquire and execute multiple sequential procedures.

Animals↗

PubMed2002

Reward-dependent spatial selectivity of anticipatory activity in monkey caudate neurons.

Many neurons show anticipatory activity in learned tasks. This phenomenon appears to reflect the brain's ability to predict future events. However, what actually is predicted is unknown. Using a memory-guided saccade task, in which only one out of four directions was rewarded in each block of trials, we found that a group of neurons in the monkey caudate nucleus (CD) showed activity before presentation of an instruction cue stimulus. Among 329 CD neurons that were related to memory-guided saccade tasks, 156 showed the precue activity and 91 of them were examined fully. Remarkably, the magnitude of the precue activity varied across the four blocks of the one-direction-rewarded (1DR) condition, depending on which direction was rewarded. A majority of neurons with precue activity (83/91, 91%) showed significant directional preference. The best and worst directions were usually in the contralateral and ipsilateral directions, respectively. Within a block, the precue activity increased rapidly for the best direction in 1DR and decreased gradually for the worst direction in 1DR and all-directions-rewarded (ADR) condition. The precue activity was weak in ADR. The precue activity did not reflect the likelihood of a particular cue stimulus, because the probability of the cue appearing in each direction was the same regardless of the rewarded direction. These results suggest that each CD neuron indicates a particular position-reward association prospectively, usually with contralateral preference. Assuming that the CD neurons have access to saccadic motor outputs, the precue activity would create a motivational bias toward the contralateral space, even before an instruction is given by the cue stimulus.

Acoustic Stimulation↗

PubMed2002

Influence of reward expectation on visuospatial processing in macaque lateral prefrontal cortex.

The lateral prefrontal cortex (LPFC) has been implicated in visuospatial processing, especially when it is required to hold spatial information during a delay period. It has also been reported that the LPFC receives information about expected reward outcome. However, the interaction between visuospatial processing and reward processing is still unclear because the two types of processing could not be dissociated in conventional delayed response tasks. To examine this, we used a memory-guided saccade task with an asymmetric reward schedule and recorded 228 LPFC neurons. The position of the target cue indicated the spatial location for the following saccade and the color of the target cue indicated the reward outcome for a correct saccade. Activity of LPFC was classified into three main types: S-type activity carried only spatial signals, R-type activity carried only reward signals, and SR-type activity carried both. Therefore only SR-type cells were potentially involved in both visuospatial processing and reward processing. SR-type activity was enhanced (SR+) or depressed (SR-) by the reward expectation. The spatial discriminability as expressed by the transmitted information was improved by reward expectation in SR+ type. In contrast, when reward information was coded by an increase of activity in the reward-absent condition (SR- type), it did not improve the spatial representation. This activity appeared to be involved in gaze fixation. These results extend previous findings suggesting that the LPFC exerts dual influences based on predicted reward outcome: improvement of memory-guided saccades (when reward is expected) and suppression of inappropriate behavior (when reward is not expected).

Animals↗

PubMed2002

Self-organization in the basal ganglia with modulation of reinforcement signals.

Self-organization is one of fundamental brain computations for forming efficient representations of information. Experimental support for this idea has been largely limited to the developmental and reorganizational formation of neural circuits in the sensory cortices. We now propose that self-organization may also play an important role in short-term synaptic changes in reward-driven voluntary behaviors. It has recently been shown that many neurons in the basal ganglia change their sensory responses flexibly in relation to rewards. Our computational model proposes that the rapid changes in striatal projection neurons depend on the subtle balance between the Hebb-type mechanisms of excitation and inhibition, which are modulated by reinforcement signals. Simulations based on the model are shown to produce various types of neural activity similar to those found in experiments.

Algorithms↗

PubMed2001

Modulation of saccadic eye movements by predicted reward outcome.

Reward is a primary goal of behavior and is crucial for survival of animals. To explore the mechanisms underlying such reward-oriented behavior, we devised a memory-guided saccade task in which only one fixed direction out of four was rewarded, which was called the one-direction-rewarded task (1DR). As the rewarded direction was changed in four blocks, saccades in a given direction were rewarded in one block (constituting reward-oriented behavior), but non-rewarded in the other blocks (non-reward-oriented behavior). As a control, an all-directions-rewarded task (ADR) was used. Using these tasks, we found that the parameters of saccades changed depending on whether or not the saccade was followed by reward. (1) The mean saccadic peak velocity was higher and the mean saccade latency was shorter in the rewarded condition than in the non-rewarded condition. (2) The mean saccade amplitude showed no difference in two out of three monkeys. (3) The variations of saccadic velocity, latency and amplitude were smaller in the rewarded condition. (4) Within a block of 1DR, the saccade velocity remained high in the rewarded condition, but decreased gradually in the non-rewarded condition; it decreased only slightly in ADR. The saccade latency showed the opposite pattern of change, but less clearly. (5) The saccades in the non-rewarded condition tended to have slower velocities and longer latencies in the trials shortly after a rewarded trial. (6) The ratio of error trials was much higher in the non-rewarded condition than the rewarded condition. (7) The errors, which were due to premature or incorrect saccades, showed unique spatiotemporal patterns that would reflect the competition between the cognitive and motivational processes. These results provide important constraints to the neuronal mechanism underlying reward-oriented behavior because it must satisfy these rules.

Animals↗